Molecules and Cells

  • 제22권2호
  • /
  • Pages.228-232
  • /
  • 2006
  • /
  • 1016-8478(pISSN)
  • /
  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
권호 표지

Ovarian Tumors in Rbp9 Mutants of Drosophila Induce an Immune Response

  • Kim, Jihyun (Department of Molecular Biology, School of Natural Sciences, Sejong University) ;
  • Kim, Chun (Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School) ;
  • Kim-Ha, Jeongsil (Department of Molecular Biology, School of Natural Sciences, Sejong University)
  • 투고 : 2006.08.08
  • 심사 : 2006.09.07
  • 발행 : 2006.10.31
⟨ 이전 논문 다음 논문 ⟩

초록

The Drosophila protein, Rbp9, is homologous to human Hu, which is reported to be involved in small cell lung cancer. Rbp9 functions in cystocyte differentiation, and mutations in Rbp9 cause ovarian tumors. Here we show that the antimicrobial peptide, Attacin, is upregulated in Rbp9 mutants, especially in ovaries where tumors form. Upregulation seems to result from activation of the NF-${\kappa}B$ pathway since we detected nuclear localization of Relish in Rbp9 mutant ovaries but not in wild type ovaries. Inactivation of NF-${\kappa}B$ in the Rbp9 mutant allows prolonged survival of malformed egg chambers. We conclude that Drosophila initiates an anti-tumor defense response via activation of NF-${\kappa}B$.

키워드

과제정보

연구 과제 주관 기관 : Korea Science and Engineering Foundation

참고문헌

  1. Akamatsu, W., Okano, H. J., Osumi, N., Inoue, T., Nakamura, S., et al. (1999) Mammalian ELAV-like neuronal RNA-binding proteins HuB and HuC promote neuronal development in both the central and the peripheral nervous systems. Proc. Natl. Acad. Sci. USA 96, 9885−9890
  2. Bulet, P., Hetru, C., Dimarcq, J. L., and Hoffmann, D. (1999) Antimicrobial peptides in insects; structure and function. Dev. Comp. Immunol. 23, 329−344
  3. Dalmau, J., Furneaux, H. M., Cordon-Cardo, C., and Posner, J. B. (1992) The expression of the Hu (paraneoplastic encephalomyelitis/ sensory neuronopath) antigen in human normal and tumor tissues. Am. J. Pathol. 141, 881−886
  4. Darnell, R. B. and DeAngelis, L. M. (1993) Regression of small-cell lung carcinoma in patients with paraneoplastic neuronal antibodies. Lancet 341, 21−22 https://doi.org/10.1016/0140-6736(93)92485-C
  5. Garg, A. and Aggarwal, B. B. (2002) Nuclear transcription factor- kappaB as a target for cancer drug development. Leukemia 16, 1053−1068 https://doi.org/10.1038/sj.leu.2402482
  6. Gerashchenko, D. and Shiromani, P. J. (2004) Effects of inflammation produced by chronic lipopolysaccharide administration on the survival of hypocretin neurons and sleep. Brain Res. 1019, 162−169 https://doi.org/10.1016/j.brainres.2004.06.016
  7. Heilborn, J. D., Nilsson, M. F., Jimenez, C. I., Sandstedt, B., Borregaard, N., et al. (2005) Antimicrobial protein hCAP18/ LL-37 is highly expressed in breast cancer and is a putative growth factor for epithelial cells. Int. J. Cancer 114, 713−719 https://doi.org/10.1002/ijc.20795
  8. Hoffmann, J. A. (1995) Innate immunity of insects. Curr. Opin. Immunol. 7, 4−10 https://doi.org/10.1016/0952-7915(95)80022-0
  9. Hojo, K., Kawamata, T., Tanaka, C., and Maeda, K. (2004) Inflammatory glial activation in the brain of a patient with hereditary sensory neuropathy type 1 with deafness and dementia. Neurosci. Lett. 367, 340−343 https://doi.org/10.1016/j.neulet.2004.06.030
  10. Kim, Y. J. and Baker, B. S. (1993) The Drosophila gene rbp9 encodes a protein that is a member of a conserved group of putative RNA binding proteins that are nervous systemspecific in both flies and humans. J. Neurosci. 13, 1045− 1056
  11. Kim, Y. S., Han, S. J., Ryu, J. H., Choi, K. H., Hong, Y. S., et al. (2000) Lipopolysaccharide-activated kinase, an essential component for the induction of the antimicrobial peptide genes in Drosophila melanogaster cells. J. Biol. Chem. 275, 2071−2079 https://doi.org/10.1074/jbc.275.3.2071
  12. Kim-Ha, J., Kim, J., and Kim, Y. J. (1999) Requirement of RBP9, a Drosophila Hu homolog, for regulation of cystocyte differentiation and oocyte determination during oogenesis. Mol. Cell. Biol. 19, 2505−2514
  13. Park, S. Y., Heo, Y. J., Kim, K. S., and Cho, Y. H. (2005) Drosophila melanogaster is susceptible to Vibrio cholerae infection. Mol. Cells 20, 409−415
  14. Shishodia, S. and Aggarwal B. B. (2004a) Nuclear factor-kappaB activation mediates cellular transformation, proliferation, invasion angiogenesis and metastasis of cancer. Cancer Treat. Res. 119, 139−173 https://doi.org/10.1007/1-4020-7847-1_8
  15. Shishodia, S. and Aggarwal B. B. (2004b) Nuclear factor-kappaB: a friend or a foe in cancer? Biochem. Pharmacol. 68, 1071− 1080 https://doi.org/10.1016/j.bcp.2004.04.026
  16. Silverman, T. and Maniatis, T. (2001) NF-kappaB signaling pathways in mammalian and insect innate immunity. Genes Dev. 15, 2321−2342 https://doi.org/10.1101/gad.909001
  17. Szabo, A., Dalmau, J., Manley, G., Rosenfeld, M., Wong, E., et al. (1991) HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal. Cell 67, 325−333 https://doi.org/10.1016/0092-8674(91)90184-Z
  18. Tzou, P., Ohresser, S., Ferrandon, D., Capovilla, M., Reichhart, J. M., et al. (2000) Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia. Immunity 13, 737−748 https://doi.org/10.1016/S1074-7613(00)00072-8